title: Anti-inflammatory modulation of immune response by probiotic Escherichia coli Nissle 1917 in human blood mononuclear cells.
abstract: Escherichia coli Nissle 1917 (EcN) bears a defect in its LPS biosynthesis leading to truncated variable oligosaccharide-antigen chains and a semi-rough phenotype. It is effectively inactivated by complement factors due to resolved serum resistance and is, therefore, safe as a probiotic strain, i.e. for the treatment of inflammatory gastrointestinal diseases. It is unknown whether the modification of LPS in EcN contributes to its probiotic properties. Purified LPS from EcN and wild-type LPS from uropathogenic E. coli W536 together with raw lysates of both strains were analyzed for their gene expression activity with human PBMCs measured by microarrays. Comparing the two LPS molecules and the two lysate variants with each other, respectively, no differences of transcriptional patterns were observed. However, when comparing LPS with lysate patterns, pro-inflammatory cytokine IL-12p40 was up-regulated by both LPS molecules and anti-inflammatory IL-10 by both lysates. The higher the lysate concentration, the higher IL-10 release from PBMCs, clearly exceeding LPS induced IL-12p40 release. Furthermore, inflammatory chemokine CCL24 (eotaxin) was down-regulated by lysates and quantitative real-time PCR revealed that EcN compared to wild-type LPS was 8 times stronger in down-regulation of CCL24. We conclude that truncated LPS may down-regulate CCL24-mediated inflammation and that EcN lysate contains as yet unidentified factors which preferably induce anti-inflammatory activity. Both effects may contribute to the probiotic properties of EcN.
authors.affiliation: Department of Experimental Pneumology, Ruhr-University Bochum, Germany.
authors.forename: Anne-Katrin
authors.initials: AK
authors.lastname: Güttsches
authors.forename: Stefan
authors.initials: S
authors.lastname: Löseke
authors.forename: Ulrich
authors.initials: U
authors.lastname: Zähringer
authors.forename: Ulrich
authors.initials: U
authors.lastname: Sonnenborn
authors.forename: Corinne
authors.initials: C
authors.lastname: Enders
authors.forename: Sören
authors.initials: S
authors.lastname: Gatermann
authors.forename: Albrecht
authors.initials: A
authors.lastname: Bufe
mesh_terms: D000893:Anti-Inflammatory Agents; D002478:Cells, Cultured; D054423:Chemokine CCL24 / Q000502:physiology; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D019286:Endopeptidase K / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000254:growth & development / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D007121:Immunocompetence / Q000187:drug effects; D017404:In Situ Hybridization, Fluorescence; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D046228:Microarray Analysis; D009000:Monocytes / Q000276:immunology*; D019936:Probiotics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000893:Anti-Inflammatory Agents; D054423:Chemokine CCL24; D018076:DNA, Complementary; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016753:Interleukin-10; D018664:Interleukin-12; D019286:Endopeptidase K